Actually, in odontology practice, the lack of bone volume limits greatly the use of dental implants. Insufficient bone volume, both in height and thickness, may result from congenital, post traumatic, surgical procedures or may result of diseases such as periodontitis. In order to solve these clinical problems, bone augmentation materials, such as autologous bone graft, demineralised bone matrix or calcium phosphate ceramics, associated with a membrane are used prior to the implantation of dental implants. Typically, the bone augmentation material is placed in fresh alveolar bone sockets, in maxillary sinus, to augment the width or height of the alveolar crest. The bone augmentation material, as filler material (i.e. autologous bone graft, calcium phosphate ceramics), helps to regenerate bone tissue while the membrane prevents the ingrowth of fibrous tissue. After a period of healing of few months, dental implants are placed in the grafted sites. The combination of a filler material and a membrane has developed the concept of guided bone tissue regeneration (GBR).
The concept of guided bone tissue regeneration (GBR) is based on the principles of tissue healing for the bone areas. It is known since the 1980's that cells that have access and can migrate into a given wound space determine the type of tissue regenerating in this space. To apply this principle to bone augmentation, barrier membranes have been used to exclude undesired cells from the wound area (fibrous cells from the connective tissue). Concomitantly, desired cells (mesenchymal and bone cells) are favoured to migrate in the defect space. In addition to barrier function and space maintenance, it has been found useful to provide the desired cells with a defined matrix so that their migration and organisation in a new bone tissue is further enhanced.
The concept of guided tissue regeneration (GTR) is frequently applied in reconstruction of periodontal defects. Membranes are used for preventing the fast growing connective tissue to invade the defect and to allow time for periodontal ligament cementum and bone regeneration.
Although the invention has been found of particular interest in the field of odontology, the invention is not limited thereto and can find advantageous applications in other fields of guided bone tissue regeneration. For example, the invention may have advantageous applications in orthopaedic or rachis surgery.
From the known products that can be used for guided bone tissue regeneration, collageneous extracellular matrix (ECM) could provide for enhancement of the migration and the organisation of cells in a new bone tissue. But the use is hampered by lack of enough stiffness for space maintenance, low availability from allogenic sources and the possibility to transfer pathogens from xenogenic sources.
Besides, some commercially available membranes for guided tissue regeneration are made of collagen from animal origin (i.e. porcine, bovine). Examples of collagen membranes are Biogide (Geistlich Pharma AG, Switzerland), Biomend (Zimmer Dental), OsseoGuard (Biomet 3i), Inion (Inion Oy, Tempere, Finland) Guidor (Guidor AB, Huddinge, Sweden). However, these barrier membranes made of collagen carry the risk of immunological rejection and disease transfer. The biodegradation of collagen membranes in the human body is variable as depending on chemical cross linking. Furthermore, the permeability to cells and tissues is not controllable as it varies from sources.
Tissue regeneration membranes made of polymers including non resorbable polytetrafluoroethylene (PTFE, Gore-Tex, W. L. Gore & Associates inc., Elkton Md., USA) and TefGen (Lifecore Biomedical, LLC, Chaska, Minn., USA) are also known. There also exist some membranes composed of resorbable polymers, such as polylactide (PLA), polyglycolide (PGA) or a mixture thereof (PLGA). Example of resorbable polylactic membranes available on the market are Epiguide or Matrix barrier (Kensey Nash Corp). However, several problems are associated with the use of these barrier membranes. Non-resorbable membranes tend to get exposed, need a second surgery to be removed and can induce cellular reactions. Resorbable membranes overcome these drawbacks but do not provide the same quality of results, especially with regards to marginal bone gain. The cause of this discrepancy is agreed to be linked to the membrane capacity of maintaining space in the defect due to weak mechanical properties.
Current membranes exhibit poor bone regeneration capacity. To overcome these problems, bone mineral (Schwarz F, Int J Oral Maxillofac Surg 2007), calcium phosphate ceramics such as hydroxyapatite (Liao S, Biomaterials 2005), tricalcium phosphate and mixtures, calcium carbonate (Fujihara K, Biomaterials 2005), have been recently incorporated into the membranes.
Most of synthetic membranes are made in the shape of porous foam, created by traditional methods, such as particulate leaching, solvent casting or gas foaming. Recently, a new technique has been introduced, which is called electrospinning or electrostatic spinning and allows the preparation of thin fibrous membranes.
Electrospinning uses a high electric voltage of few kilovolts to draw a polymer solution or polymer melts into a whipped jet, a syringe or a capillary tube. A polymer jet is ejected from the charged polymer solution under the influence of applied electrical field. Ultrafine fibers deposit on a collector attached to the ground in the form of a non-woven structure. Fibers obtained from electrospinning exhibit diameters in the range of 50 nm to a few microns.
In order to stimulate bone formation, electrospun polycaprolactone (PCL) nano-hydroxyapatite membranes have been recently prepared (Yang F, Acta Biomaterialia 2009). Nanometer sized hydroxyapatite particles were suspended in 2,2,2-trifluoroethanol (TFE) solvent and water by ultrasonic and vigorous stirring before adding PCL polymer. Surfactant dioctyl sulfosuccinate sodium salt was dissolved in the solvent to obtain a stable particle suspension in the polymer solution. A voltage of 18-22 kV was applied to generate a polymer jet in the electro spinning set up. The resulting fibers were collected on a rotating mandrel. Previous published studies have demonstrated cell proliferation on these electrospun nanofiber membranes but not cell penetration. Furthermore, no proof of efficacy in vivo could be demonstrated with these electrospun PCL-nHA membranes.
Another membrane comprising a porous semi-permeable layer and a fibrillar layer formed by electrospinning is known from WO-A-2009/054609.
However, the known electrospun membranes do not allow suitable cell penetration or cell migration across the fibers to permit the formation of a mineralised matrix and therefore of bone tissue. The spaces between electrospun fibers are not sufficient for cell invasion. Typically, the size of a cell is around 10 μm and the space between electrospun fibers is lower than the size of a cell, thus preventing cellular invasion, cell ingrowth or cell colonization into the implantable device.